Kure Medical Center

In Japan, the implantation of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) is not covered by insurance reimbursement, and the underuse of ICDs has been noted. Therefore, this study analyzed the medical costs incurred due to a lack of primary prevention ICD therapy for SCD. This retrospective cohort study analyzed data from 4 advanced critical care centers between January 2020 and December 2024. From a database of 3,606 cases of cardiac arrest, there were 348 patients with a documented rhythm at the time of arrest that could have been treated with an ICD. Of these patients, 43 (12.4%) had documented evidence of heart failure treatment and were eligible for ICD implantation before experiencing a cardiac arrest. The total mean (±SD) medical cost for these patients was US $11,679±14,666 (¥1,775,150±2,229,272). In this multicenter retrospective analysis, we identified a subset of patients who were eligible for primary prevention ICD therapy but did not receive it prior to experiencing sudden cardiac arrest. These cases were associated with substantial post-arrest medical costs. Our findings highlight the potential clinical and economic impact of the underutilization of ICDs in Japan and suggest that broader implementation of guideline-directed ICD therapy for primary prevention may reduce both mortality and healthcare expenditure.

Recent studies have demonstrated that breast pathological complete response (pCR) can be accurately diagnosed preoperatively using image-guided needle biopsy after neoadjuvant chemotherapy (NAC), underscoring the value of incorporating ypT stage into prediction models for axillary response (ypN0). Based on this evidence, we developed and externally validated a nomogram to predict ypN0 in patients with clinically node-positive (cN+) breast cancer treated with NAC. This retrospective, multicenter study included 609 patients with cN + breast cancer who underwent NAC followed by surgery. A nomogram was developed using a training cohort (n = 330) and validated in an independent cohort (n = 279). Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, decision curve analysis (DCA), and positive predictive value (PPV). The nomogram incorporated five predictors: ypT stage, cN stage, hormone receptor status, HER2 status, and post-NAC cN stage. It showed strong discriminative ability, with bias-corrected AUCs of 0.858 in the training cohort and 0.855 in the validation cohort. Calibration and DCA confirmed good model performance. PPV exceeded 0.90 when the nomogram-predicted probability was ≥ 0.7 in both cohorts. This nomogram demonstrated high diagnostic accuracy for predicting ypN0 and may support the selection of candidates for axillary surgery de-escalation based on post-NAC biopsy findings. Prospective validation using biopsy-confirmed pCR is warranted.

Abstract We analyzed the differences in bacterial composition between 475 Japanese patients with advanced gastric cancer (median age 70 years, median BMI 20.0) and 106 healthy individuals using a comprehensive metagenome shotgun analysis. Among the patients with advanced gastric cancer, 71% were male, 37.% patients had relapsed, and 55.5% previously underwent gastrectomy. Bifidobacterium , Anaerostipes , and Parabacteroides were predominant in healthy individuals, whereas Streptococcus , Lactobacillus , and Odoribacter were predominant in patients with advanced gastric cancer. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that butanoate and pyruvate metabolism was enriched in healthy individuals, whereas factors such as ABC transporters and ribosomes were enriched in patients with advanced gastric cancer. Clustering analysis broadly classified patients with advanced gastric cancer and healthy individuals into two clusters; however, clustering using pathway data enabled a clearer classification of patients with advanced gastric cancer and healthy individuals than clustering using flora analysis. Moreover, healthy individuals showed higher bacterial flora diversity than patients with advanced gastric cancer. Thus, we successfully identified the molecular characteristics of microbial genera and functional pathways in the gut of patients with advanced gastric cancer. Our results suggest that fecal metagenomic shotgun sequencing analysis can be used to detect gastric cancer.

Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHHs) over 32 days post-inoculation (p.i.) and modified our in-vivo agent-based modeling (ABM) to gain insights into the HBV lifecycle and spread in vitro. Parallel PHH cultures were mock-treated or treated with HBV entry inhibitor Myr-preS1 (6.25 µg/mL) was initiated 24 h p.i. In untreated PHH, three viral DNA kinetic patterns were identified: (i) an initial decline, followed by (ii) rapid amplification and (iii) slower amplification/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to naïve cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 h. After the eclipse phase, the viral production rate increased over time, starting with a slow production cycle of 1 virion per day, which gradually accelerated to 1 virion per hour after 3 days. Approximately 4 days later, virion production reached a steady state production rate of 4 virions/h. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90-92%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar to those predicted in uPA/SCID mice with human livers.IMPORTANCEWhile primary human hepatocytes (PHHs) are the most physiologically relevant culture system for studying HBV infection in vitro, a comprehensive understanding of HBV infection kinetics and spread in PHH is lacking. In this study, we characterize HBV viral kinetics and modify our in vivo agent-based modeling (ABM) to provide quantitative insights into the HBV production cycle and viral spread in PHH. The ABM provides an estimate of the HBV eclipse phase duration, HBV production cycles, and Myr-preS1 efficacy in blocking HBV spread in PHH. The results resemble those predicted in uPA/SCID mice with human livers, demonstrating that estimated HBV infection kinetic parameters in PHH in vitro mirror those observed in the in vivo HBV infection chimeric mouse model.

Background/Objectives: We define severe postpartum hemorrhage (PPH) with macroscopic hematuria as clinical disseminated intravascular coagulation (DIC), a life-threatening condition. We also report a methodology using machine learning, a subtype of artificial intelligence, for developing the boundary criterion for predicting hematuria on the fibrinogen-fibrin/fibrinogen degradation product (FDP) plane. A positive FDP-fibrinogen/3-60 (mg/dL) value indicates hematuria; otherwise, non-hematuria is observed. We aimed to validate this criterion using severe placental abruption (PA), and to examine the activation of the coagulation-fibrinolytic system in clinical DIC. Methods: Of 17,285 deliveries across nine perinatal centers in Japan between 2020 and 2024, 13 had severe PA without hematuria, 18 had severe PPH without hematuria, and 3 had severe PPH with hematuria, i.e., clinical DIC. We calculated the values of the criterion formula for 13 cases of severe PA to validate the boundary criterion and compared the laboratory tests for coagulation-fibrinolytic activation among the three groups. Results: The calculated values using the criterion for the 13 PA without hematuria ranged from -108.91 to -5.87 and all were negative. In cases of clinical DIC, fibrinogen levels (median, 62 mg/dL) were lower (p < 0.05), while levels of FDP (96 mg/dL), the thrombin-antithrombin complex (120 ng/mL), and the plasmin-α2-plasmin inhibitor complex (28.4 μg/mL) were significantly higher than in the other two groups. Conclusions: This study demonstrated the validity of the boundary criterion for predicting hematuria using severe PA. The coagulation-fibrinolytic test results suggested that PPH cases with hematuria were assumed to have clinical DIC, indicating that this criterion may be considered for diagnosing DIC during delivery. However, further additional patient data are needed to confirm the usefulness of this criterion because of the very low number of hematuria cases.

Elevated serum IgG4 is a key diagnostic marker for type 1 autoimmune pancreatitis (AIP), but some patients lack IgG4 elevation, complicating diagnosis. This study investigated the clinicopathological features of AIP without elevated serum IgG4 levels. A total of 323 patients diagnosed with AIP at Hiroshima University Hospital and affiliated institutions were analyzed. Patients were categorized into IgG4-positive (≥ 135 mg/dL), IgG4-negative (< 135 mg/dL with “definite” or “probable” diagnosis), and possible (with “possible” diagnosis) groups. Comparative analysis was performed between the IgG4-positive (n = 281) and IgG4-negative (n = 20) groups. Segmental or focal narrowing of the main pancreatic duct (MPD) and retroperitoneal fibrosis were significantly more common in the IgG4-negative group (90.0% vs. 58.7%, P = 0.011; and 35.0% vs. 12.5%, P = 0.012, respectively). Although the number of pathological findings was comparable, the rate of surgical intervention was significantly higher in the IgG4-negative group (P < 0.001). No significant differences were observed in relapse rates or relapse sites between the two groups. These findings suggest that MPD narrowing and retroperitoneal fibrosis may be characteristic of AIP without elevated IgG4. Vigilant monitoring for relapse is warranted, regardless of serum IgG4 levels.